UA72340C2 - Способ получения циталопрама - Google Patents
Способ получения циталопрама Download PDFInfo
- Publication number
- UA72340C2 UA72340C2 UA2003010797A UA200310797A UA72340C2 UA 72340 C2 UA72340 C2 UA 72340C2 UA 2003010797 A UA2003010797 A UA 2003010797A UA 200310797 A UA200310797 A UA 200310797A UA 72340 C2 UA72340 C2 UA 72340C2
- Authority
- UA
- Ukraine
- Prior art keywords
- formula
- compound
- citalopram
- alkylamino
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 34
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 title claims abstract description 33
- 229960001653 citalopram Drugs 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 12
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 12
- QTWUWCFGWYYRRL-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(=O)OCC2=C1 QTWUWCFGWYYRRL-UHFFFAOYSA-N 0.000 claims abstract description 9
- -1 cyano, hydroxy Chemical group 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000012024 dehydrating agents Substances 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 230000003993 interaction Effects 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 229940124530 sulfonamide Drugs 0.000 claims description 7
- 150000003456 sulfonamides Chemical class 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 4
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 2
- 238000006798 ring closing metathesis reaction Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 150000002367 halogens Chemical group 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000654 additive Substances 0.000 description 5
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 238000003747 Grignard reaction Methods 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 3
- 229910001623 magnesium bromide Inorganic materials 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- WSEQXVZVJXJVFP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 WSEQXVZVJXJVFP-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- KTGRHKOEFSJQNS-UHFFFAOYSA-N Citalopram Oxalate Chemical compound OC(=O)C(O)=O.O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 KTGRHKOEFSJQNS-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 2
- RYEXTBOQKFUPOE-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].CC[CH2-] RYEXTBOQKFUPOE-UHFFFAOYSA-M 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- ARCGXLSVLAOJQL-UHFFFAOYSA-N trimellitic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 description 2
- YXCRMKYHFFMNPT-UHFFFAOYSA-N 1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound C1=CC(F)=CC=C1C1C2=CC=C(C#N)C=C2CO1 YXCRMKYHFFMNPT-UHFFFAOYSA-N 0.000 description 1
- GECQEQCYCDJXJC-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carboxylic acid Chemical compound O1CC2=CC(C(O)=O)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 GECQEQCYCDJXJC-UHFFFAOYSA-N 0.000 description 1
- XEEGWTLAFIZLSF-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2C(=O)OCC2=C1 XEEGWTLAFIZLSF-UHFFFAOYSA-N 0.000 description 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
- IUSPXLCLQIZFHL-UHFFFAOYSA-N 5-bromo-3h-2-benzofuran-1-one Chemical compound BrC1=CC=C2C(=O)OCC2=C1 IUSPXLCLQIZFHL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 101100412856 Mus musculus Rhod gene Proteins 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 101100242191 Tetraodon nigroviridis rho gene Proteins 0.000 description 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- ALIGTYPNWJPIKT-UHFFFAOYSA-M [Cl-].FC1=CC=C([Mg+])C=C1 Chemical compound [Cl-].FC1=CC=C([Mg+])C=C1 ALIGTYPNWJPIKT-UHFFFAOYSA-M 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LEKPFOXEZRZPGW-UHFFFAOYSA-N copper;dicyanide Chemical compound [Cu+2].N#[C-].N#[C-] LEKPFOXEZRZPGW-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical class C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
- Furan Compounds (AREA)
Abstract
Раскрыт способ получения циталопрама, который включает взаимодействие 5-карбоксифталидуа последовательно с 4-галогенфторфенилом реактива Гриньяра и с 3-галоген-N,N-диметилпропиламином реактива Гриньяра и последующее замыкание цикла полученного соединения формулы XI к соединению формулы IV с последующим преобразованием соединения формулы IV в циталопрам. Также раскрыты способы получения и преобразования соединения формулы IV.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DKPA200001231 | 2000-08-18 | ||
PCT/DK2001/000542 WO2002016342A1 (en) | 2000-08-18 | 2001-08-14 | Method for the preparation of citalopram |
Publications (1)
Publication Number | Publication Date |
---|---|
UA72340C2 true UA72340C2 (ru) | 2005-02-15 |
Family
ID=8159660
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA2003010798A UA71676C2 (en) | 2000-08-18 | 2001-08-14 | A method for the preparation of citalopram |
UA2003010797A UA72340C2 (ru) | 2000-08-18 | 2001-08-14 | Способ получения циталопрама |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA2003010798A UA71676C2 (en) | 2000-08-18 | 2001-08-14 | A method for the preparation of citalopram |
Country Status (41)
Country | Link |
---|---|
US (2) | US6509483B2 (ru) |
EP (2) | EP1309582B1 (ru) |
JP (2) | JP2004506729A (ru) |
KR (2) | KR100887207B1 (ru) |
CN (3) | CN1239490C (ru) |
AR (3) | AR029597A1 (ru) |
AT (4) | ATE281447T1 (ru) |
AU (6) | AU2001279609B2 (ru) |
BE (2) | BE1013443A6 (ru) |
BG (2) | BG65965B1 (ru) |
CA (2) | CA2354877C (ru) |
CH (2) | CH691968A5 (ru) |
CL (2) | CL2008002412A1 (ru) |
CZ (2) | CZ295863B6 (ru) |
DE (4) | DE60106932T2 (ru) |
DK (4) | DK200101219A (ru) |
EA (2) | EA005946B1 (ru) |
ES (4) | ES2230347T3 (ru) |
FI (2) | FI20011621A (ru) |
FR (2) | FR2813078B1 (ru) |
GB (2) | GB2362647B (ru) |
GR (1) | GR1004074B (ru) |
HK (3) | HK1044538B (ru) |
HR (2) | HRP20030064A2 (ru) |
HU (2) | HUP0103291A3 (ru) |
IE (2) | IES20010760A2 (ru) |
IL (2) | IL144816A (ru) |
IS (2) | IS2121B (ru) |
ME (2) | MEP2308A (ru) |
MX (2) | MXPA03001329A (ru) |
NL (2) | NL1018776C1 (ru) |
NO (2) | NO326772B1 (ru) |
NZ (2) | NZ523853A (ru) |
PL (2) | PL359825A1 (ru) |
PT (2) | PT1309582E (ru) |
RS (2) | RS50258B (ru) |
SI (2) | SI1309582T1 (ru) |
SK (2) | SK287008B6 (ru) |
UA (2) | UA71676C2 (ru) |
WO (2) | WO2002016341A1 (ru) |
ZA (1) | ZA200106683B (ru) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR022329A1 (es) | 1999-01-29 | 2002-09-04 | Lundbeck & Co As H | Metodo para la preparacion de 5-cianoftalida |
ES2195554T5 (es) * | 1999-04-14 | 2010-02-02 | H. Lundbeck A/S | Metodo para la preparacion de citalopram. |
ITMI991581A1 (it) * | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
TR200401456T1 (tr) | 1999-10-25 | 2005-04-21 | H. Lundbeck A/S | Sitalopram hazırlanması için yöntem. |
AR026063A1 (es) | 1999-11-01 | 2002-12-26 | Lundbeck & Co As H | Metodo para la preparacion de 5-carboxiftalida. |
NZ519739A (en) | 1999-12-28 | 2004-03-26 | H | Method for the preparation of citalopram |
IL150367A0 (en) | 1999-12-30 | 2002-12-01 | Lundbeck & Co As H | Method for the preparation of citalopram |
EA005134B1 (ru) * | 2000-01-14 | 2004-12-30 | Х.Лундбекк А/С | Способ получения 5-цианофталида |
IES20010157A2 (en) | 2000-03-03 | 2002-03-06 | Lundbeck & Co As H | Method for the preparation of citalopram |
NL1017500C1 (nl) | 2000-03-13 | 2001-04-26 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
CA2402553A1 (en) * | 2000-03-13 | 2001-09-20 | H. Lundbeck A/S | Stepwise alkylation of 5-substituted 1-(4-fluorophenyl)-1,3-dihydroisobenzofurans |
HUP0300274A2 (hu) | 2000-03-13 | 2003-06-28 | H. Lundbeck A/S | Eljárás citalopram előállítására |
CN1418205A (zh) | 2000-03-14 | 2003-05-14 | H·隆德贝克有限公司 | 制备西酞普兰的方法 |
HUP0300134A2 (en) * | 2000-03-16 | 2003-05-28 | Lundbeck & Co As H | Method for the preparation of 5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofurans |
AR032455A1 (es) | 2000-05-12 | 2003-11-12 | Lundbeck & Co As H | Metodo para la preparacion de citalopram, un intermediario empleado en el metodo, un metodo para la preparacion del intermediario empleado en el metodo y composicion farmaceutica antidepresiva |
FI20011621A (fi) | 2000-08-18 | 2002-02-19 | Lundbeck & Co As H | Menetelmä sitalopraamin valmistamiseksi |
PT1181713E (pt) | 2000-12-22 | 2005-02-28 | Lundbeck & Co As H | Metodo para preparacao de citalopram puro |
US7148364B2 (en) * | 2002-01-07 | 2006-12-12 | Sun Pharmaceutical Industries | Process for the preparation of 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile |
PE20040991A1 (es) | 2002-08-12 | 2004-12-27 | Lundbeck & Co As H | Separacion de intermediarios para la preparacion de escitalopram |
TR200504022T1 (tr) * | 2003-03-24 | 2006-08-21 | Hetero Drugs Limited | (S)-sitalopram oksalatın yeni sıvı kristal formları. |
US20050143350A1 (en) * | 2003-11-19 | 2005-06-30 | Seed John C. | Combination drug therapy to treat obesity |
CN100569765C (zh) | 2003-12-19 | 2009-12-16 | 杭州民生药业集团有限公司 | 西酞普兰中间体晶体碱 |
US9339500B2 (en) * | 2008-03-04 | 2016-05-17 | Intra-Cellular Therapies, Inc. | Methods of treating vasomotor symptoms |
US20100087664A1 (en) * | 2008-10-07 | 2010-04-08 | Ravindra Vedantham | Preparation of citalopram and salts thereof |
JP6222973B2 (ja) * | 2013-04-19 | 2017-11-01 | 日本テルペン化学株式会社 | ジベンジルトリチオカーボネート誘導体 |
CN103936702A (zh) * | 2014-05-07 | 2014-07-23 | 成都诺维尔生物医药有限公司 | 艾司西酞普兰杂质j的合成方法 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1143702A (ru) | 1965-03-18 | |||
GB1526331A (en) * | 1976-01-14 | 1978-09-27 | Kefalas As | Phthalanes |
GB8419963D0 (en) | 1984-08-06 | 1984-09-12 | Lundbeck & Co As H | Intermediate compound and method |
GB8814057D0 (en) | 1988-06-14 | 1988-07-20 | Lundbeck & Co As H | New enantiomers & their isolation |
DE3926765A1 (de) | 1989-08-12 | 1991-02-14 | Hoechst Ag | Verfahren zur verminderung von primaerem und sekundaerem amin in einem tertiaeren amin |
DK213290D0 (da) | 1990-09-06 | 1990-09-06 | Lundbeck & Co As H | Treatment of cerebrovascular disorders |
US5296507A (en) | 1990-09-06 | 1994-03-22 | H.Lundbeck A/S | Treatment of cerbrovascular disorders |
DE19626659A1 (de) | 1996-07-03 | 1998-01-08 | Basf Ag | Verfahren zur Herstellung von Phthaliden |
DE19627697A1 (de) | 1996-07-10 | 1998-01-15 | Basf Ag | Verfahren zur Herstellung von Phthaliden |
ZA9711376B (en) | 1996-12-20 | 1998-07-21 | Lundbeck & Co As H | Indole or dihydroindole derivatives |
PT1015416E (pt) * | 1997-07-08 | 2002-03-28 | Lundbeck & Co As H | Metodo para a producao de citalopram |
UA62985C2 (en) * | 1997-11-10 | 2004-01-15 | Lunnbeck As H | A method for the preparation of citalopram |
JP3813820B2 (ja) | 1997-11-11 | 2006-08-23 | ハー・ルンドベック・アクチエゼルスカベット | シタロプラムの製造方法 |
EP1123284B1 (en) | 1998-10-20 | 2003-01-08 | H. Lundbeck A/S | Method for the preparation of citalopram |
ES2195644T3 (es) * | 1998-12-23 | 2003-12-01 | Lundbeck & Co As H | Metodo para la preparacion de 5-cianoftalida. |
AR022329A1 (es) | 1999-01-29 | 2002-09-04 | Lundbeck & Co As H | Metodo para la preparacion de 5-cianoftalida |
ES2195554T5 (es) | 1999-04-14 | 2010-02-02 | H. Lundbeck A/S | Metodo para la preparacion de citalopram. |
ITMI991579A1 (it) | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
ITMI991581A1 (it) * | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
CH692421A5 (de) | 1999-10-25 | 2002-06-14 | Lundbeck & Co As H | Verfahren zur Herstellung von Citalopram. |
US6310222B1 (en) | 1999-11-01 | 2001-10-30 | Sumika Fine Chemicals Co., Ltd. | Production method of 5-phthalancarbonitrile compound, intermediate therefor and production method of the intermediate |
IES20010143A2 (en) | 2000-02-24 | 2001-07-25 | Lundbeck & Co As H | Method for the preparation of citalopram |
FR2805812A1 (fr) | 2000-02-24 | 2001-09-07 | Lundbeck & Co As H | Procede de preparation du citalopram |
GB0005477D0 (en) * | 2000-03-07 | 2000-04-26 | Resolution Chemicals Limited | Process for the preparation of citalopram |
FI20011621A (fi) | 2000-08-18 | 2002-02-19 | Lundbeck & Co As H | Menetelmä sitalopraamin valmistamiseksi |
PT1181713E (pt) | 2000-12-22 | 2005-02-28 | Lundbeck & Co As H | Metodo para preparacao de citalopram puro |
PT1181272E (pt) | 2000-12-28 | 2003-01-31 | Lundbeck & Co As H | Processo para a preparacao de citalopram puro |
-
2001
- 2001-08-09 FI FI20011621A patent/FI20011621A/fi unknown
- 2001-08-09 IL IL14481601A patent/IL144816A/xx not_active IP Right Cessation
- 2001-08-09 CA CA002354877A patent/CA2354877C/en not_active Expired - Fee Related
- 2001-08-09 CA CA002354880A patent/CA2354880C/en not_active Expired - Fee Related
- 2001-08-09 IL IL14481701A patent/IL144817A0/xx not_active IP Right Cessation
- 2001-08-09 FI FI20011622A patent/FI20011622A/fi unknown
- 2001-08-10 HU HU0103291A patent/HUP0103291A3/hu unknown
- 2001-08-10 IS IS6048A patent/IS2121B/is unknown
- 2001-08-10 IS IS6047A patent/IS2120B/is unknown
- 2001-08-13 IE IE20010760A patent/IES20010760A2/en not_active IP Right Cessation
- 2001-08-13 HU HU0103295A patent/HUP0103295A3/hu unknown
- 2001-08-13 IE IE20010761A patent/IES20010761A2/en not_active IP Right Cessation
- 2001-08-14 US US09/930,110 patent/US6509483B2/en not_active Expired - Fee Related
- 2001-08-14 DK DK200101219A patent/DK200101219A/da not_active Application Discontinuation
- 2001-08-14 AU AU2001279609A patent/AU2001279609B2/en not_active Ceased
- 2001-08-14 KR KR1020037001900A patent/KR100887207B1/ko not_active IP Right Cessation
- 2001-08-14 UA UA2003010798A patent/UA71676C2/uk unknown
- 2001-08-14 JP JP2002521442A patent/JP2004506729A/ja not_active Withdrawn
- 2001-08-14 AT AT01957785T patent/ATE281447T1/de not_active IP Right Cessation
- 2001-08-14 EA EA200300279A patent/EA005946B1/ru not_active IP Right Cessation
- 2001-08-14 GB GB0119733A patent/GB2362647B/en not_active Expired - Fee Related
- 2001-08-14 PL PL35982501A patent/PL359825A1/xx not_active Application Discontinuation
- 2001-08-14 WO PCT/DK2001/000541 patent/WO2002016341A1/en active IP Right Grant
- 2001-08-14 EA EA200300277A patent/EA005811B1/ru not_active IP Right Cessation
- 2001-08-14 PT PT01957786T patent/PT1309582E/pt unknown
- 2001-08-14 US US09/930,107 patent/US6426422B1/en not_active Expired - Fee Related
- 2001-08-14 SI SI200130272T patent/SI1309582T1/xx unknown
- 2001-08-14 NO NO20013942A patent/NO326772B1/no not_active IP Right Cessation
- 2001-08-14 DE DE60106932T patent/DE60106932T2/de not_active Expired - Lifetime
- 2001-08-14 ME MEP-23/08A patent/MEP2308A/xx unknown
- 2001-08-14 NZ NZ523853A patent/NZ523853A/en unknown
- 2001-08-14 NZ NZ523877A patent/NZ523877A/en unknown
- 2001-08-14 AT AT01957786T patent/ATE281448T1/de not_active IP Right Cessation
- 2001-08-14 JP JP2002521443A patent/JP2004506730A/ja not_active Withdrawn
- 2001-08-14 DK DK01957786T patent/DK1309582T3/da active
- 2001-08-14 AU AU2001279608A patent/AU2001279608B2/en not_active Ceased
- 2001-08-14 ZA ZA200106683A patent/ZA200106683B/xx unknown
- 2001-08-14 RS YU6903A patent/RS50258B/sr unknown
- 2001-08-14 EP EP01957786A patent/EP1309582B1/en not_active Expired - Lifetime
- 2001-08-14 DK DK200101216A patent/DK200101216A/da not_active Application Discontinuation
- 2001-08-14 EP EP01957785A patent/EP1309581B1/en not_active Expired - Lifetime
- 2001-08-14 AU AU7960801A patent/AU7960801A/xx active Pending
- 2001-08-14 MX MXPA03001329A patent/MXPA03001329A/es active IP Right Grant
- 2001-08-14 DK DK01957785T patent/DK1309581T3/da active
- 2001-08-14 SI SI200130273T patent/SI1309581T1/xx unknown
- 2001-08-14 AU AU7960901A patent/AU7960901A/xx active Pending
- 2001-08-14 PL PL35996901A patent/PL359969A1/xx not_active Application Discontinuation
- 2001-08-14 DE DE60106933T patent/DE60106933T2/de not_active Expired - Lifetime
- 2001-08-14 ME MEP-22/08A patent/MEP2208A/xx unknown
- 2001-08-14 NO NO20013943A patent/NO326570B1/no not_active IP Right Cessation
- 2001-08-14 SK SK322-2003A patent/SK287008B6/sk not_active IP Right Cessation
- 2001-08-14 GR GR20010100398A patent/GR1004074B/el unknown
- 2001-08-14 RS YUP-115/03A patent/RS50287B/sr unknown
- 2001-08-14 WO PCT/DK2001/000542 patent/WO2002016342A1/en active IP Right Grant
- 2001-08-14 ES ES01957785T patent/ES2230347T3/es not_active Expired - Lifetime
- 2001-08-14 PT PT01957785T patent/PT1309581E/pt unknown
- 2001-08-14 UA UA2003010797A patent/UA72340C2/ru unknown
- 2001-08-14 GB GB0119734A patent/GB2365865B/en not_active Expired - Fee Related
- 2001-08-14 MX MXPA03000913A patent/MXPA03000913A/es active IP Right Grant
- 2001-08-14 KR KR1020037002005A patent/KR100887206B1/ko not_active IP Right Cessation
- 2001-08-14 SK SK320-2003A patent/SK287236B6/sk not_active IP Right Cessation
- 2001-08-14 ES ES01957786T patent/ES2228920T3/es not_active Expired - Lifetime
- 2001-08-15 CZ CZ20012959A patent/CZ295863B6/cs not_active IP Right Cessation
- 2001-08-15 CZ CZ20012958A patent/CZ294746B6/cs not_active IP Right Cessation
- 2001-08-15 AU AU2001100271A patent/AU2001100271B4/en not_active Expired
- 2001-08-16 AU AU2001100278A patent/AU2001100278B4/en not_active Expired
- 2001-08-16 CH CH01521/01A patent/CH691968A5/de not_active IP Right Cessation
- 2001-08-16 FR FR0110857A patent/FR2813078B1/fr not_active Expired - Fee Related
- 2001-08-16 AR ARP010103923A patent/AR029597A1/es not_active Application Discontinuation
- 2001-08-16 DE DE10140028A patent/DE10140028A1/de not_active Withdrawn
- 2001-08-16 DE DE10140029A patent/DE10140029A1/de not_active Withdrawn
- 2001-08-16 NL NL1018776A patent/NL1018776C1/nl not_active IP Right Cessation
- 2001-08-16 AR ARP010103924A patent/AR029598A1/es not_active Application Discontinuation
- 2001-08-16 CH CH01522/01A patent/CH691969A5/de not_active IP Right Cessation
- 2001-08-16 NL NL1018775A patent/NL1018775C1/nl not_active IP Right Cessation
- 2001-08-16 BE BE2001/0548A patent/BE1013443A6/fr not_active IP Right Cessation
- 2001-08-16 FR FR0110855A patent/FR2813077B1/fr not_active Expired - Fee Related
- 2001-08-17 CN CNB2004100018711A patent/CN1239490C/zh not_active Expired - Fee Related
- 2001-08-17 ES ES200101920A patent/ES2170735B2/es not_active Expired - Fee Related
- 2001-08-17 CN CNB011339489A patent/CN1222517C/zh not_active Expired - Fee Related
- 2001-08-17 AT AT0065001U patent/AT4946U1/de not_active IP Right Cessation
- 2001-08-17 CN CNB011339470A patent/CN1159307C/zh not_active Expired - Fee Related
- 2001-08-17 ES ES200101919A patent/ES2170734B2/es not_active Expired - Fee Related
- 2001-08-17 AT AT0065101U patent/AT5026U1/de not_active IP Right Cessation
- 2001-08-20 BE BE2001/0550A patent/BE1013444A6/fr not_active IP Right Cessation
-
2002
- 2002-08-22 HK HK02106176.1A patent/HK1044538B/zh not_active IP Right Cessation
- 2002-09-04 HK HK05100254A patent/HK1068069A1/xx not_active IP Right Cessation
- 2002-09-04 HK HK02106522.2A patent/HK1047086B/zh not_active IP Right Cessation
-
2003
- 2003-02-03 HR HR20030064A patent/HRP20030064A2/xx not_active Application Discontinuation
- 2003-02-03 HR HR20030065A patent/HRP20030065A2/xx not_active Application Discontinuation
- 2003-02-24 BG BG107584A patent/BG65965B1/bg unknown
- 2003-02-24 BG BG107583A patent/BG65964B1/bg unknown
-
2008
- 2008-04-25 AR ARP080101772A patent/AR066694A2/es unknown
- 2008-08-14 CL CL2008002412A patent/CL2008002412A1/es unknown
- 2008-09-09 CL CL2008002673A patent/CL2008002673A1/es unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
UA72340C2 (ru) | Способ получения циталопрама | |
US6365747B1 (en) | Method for the preparation of citalopram | |
EP1173431B2 (en) | Method for the preparation of citalopram | |
JP3526581B2 (ja) | シタロプラムの製造方法 | |
JP3447267B2 (ja) | シタロプラムの製造方法 | |
AU2001279609A1 (en) | Method for the preparation of citalopram | |
US6660873B2 (en) | Method for the preparation of citalopram | |
ITMI20011786A1 (it) | Metodo per la preparazione di citalopram | |
BG64446B1 (en) | Method for the preparation of citalopram, intermediates for its materialization and antidepressive agent | |
ZA200107956B (en) | Method for the preparation of citalopram. |